Scientists reported Wednesday that they genetically modified stem cells to grow skin that they successfully grafted over nearly all of a child's body — a remarkable achievement that could revolutionize treatment of burn victims and people with skin diseases.

The research, published in the journal Nature, involved a 7-year-old boy who suffers from a genetic disease known as junctional epidermolysis bullosa (JEB) that makes skin so fragile that minor friction such as rubbing causes the skin to blister or come apart.

By the time the boy arrived at Children's Hospital of Ruhr-University in Germany in 2015, he was gravely ill. Doctors noted that he had “complete epidural loss” on about 60 percent of his body surface area, was in so much pain that he was on morphine, and fighting off a systemic staph infection. The doctors tried everything they could think of: antibiotics, changing dressings, grafting skin donated by his father. But nothing worked, and they told his parents to prepare for the worst.

“We had a lot of problems in the first days keeping this kid alive,” Tobias Hirsch, one of the treating physicians, recalled in a conference call with reporters this week.

Gene therapy to treat a skin disease. (Nature News & Views)

Hirsch and his colleague Tobias Rothoeft began to scour the medical literature for anything that might help and came across an article describing a highly experimental procedure to genetically engineer skin cells. They contacted the author, Michele De Luca, of the Center for Regenerative Medicine at the University of Modena and Reggio Emilia in Italy. De Luca flew out right away.

Using a technique he had used only twice before and even then only on small parts of the body, De Luca harvested cells from a four-square-centimeter patch of skin on an unaffected part of the boy's body and brought them into the lab. There, he genetically modified them so that they no longer contained the mutated form of a gene known to cause the disease and grew the cells into patches of genetically modified epidermis. They discovered, the researchers reported, that “the human epidermis is sustained by a limited number of long-lived stem cells which are able to extensively self-renew.”

In three surgeries, the child's doctors took that lab-grown skin and used it to cover nearly 80 percent of the boy's body — mostly on the limbs and on his back, which had suffered the most damage. The procedure was permitted under a “compassionate use” exception that allows researchers under certain dire circumstances to make a treatment available even though it is not approved by regulators for general use. Then, over the course of the next eight months while the child was in the intensive care unit, they watched and waited.

The boy's recovery was stunning.

The regenerated epidermis “firmly adhered to the underlying dermis,” the researchers reported. Hair follicles grew out of some areas. And even bumps and bruises healed normally. Unlike traditional skin grafts that require ointment once or twice a day to remain functional, the boy's new skin was fine with the normal amount of washing and moisturizing.

“The epidermis looks basically normal. There is no big difference,” De Luca said. He said he expects the skin to last “basically the life of the patient.”

In an analysis accompanying the main article in Nature, Mariacelest Aragona and Cedric Blanpain wrote that this therapy appears to be one of the few examples of truly effective stem-cell therapies. The study “demonstrates the feasibility and safety of replacing the entire epidermis using combined stem-cell and gene therapy,” and also provides important insights into how different types of cells work together to help our skin renew itself.

They said there are still many other lingering questions, including whether such procedures might work better in children than adults and whether there would be longer-term adverse consequences, such as the development of cancer.

There are also many challenges to translating this research to treating wounds sustained in fires or other violent ways. In the skin disease that was treated in the boy, the epidermis is damaged but the layer beneath it, the dermis, is intact. The dermis is what the researchers called an ideal receiving bed for the lab-grown skin. But if deeper layers of the skin are burned or torn off, it's possible that the artificial skin would not adhere as well.

“No matter how you prepare, it’s a bad situation,” De Luca said. For the time being, he says he's continuing to study the procedure in two clinical trials that involve genetic diseases.

Meanwhile, Hirsch and Rothoeft report that the boy is continuing to do well and is not on any medication for the first time in many years. Doctors are carefully monitoring the child for any signs that there may be some cells that were not corrected and that the disease may reemerge, but right now that does not appear to be happening in the transplanted areas. However, the child does have some blistering in about 2 to 3 percent of his body in non-grafted areas, and they are considering whether to replace that skin as well.

But for now, they are giving the boy time to be a boy, Rothoeft said: “The kid is now back to school and plays soccer and spends other days with the children.”

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